Myelin, Movement, and the Mind: Hot Topics in MS Research
Myelin Repair and Stem Cells
Remarkable progress has been made in the last 25 years in treating relapsing-remitting multiple sclerosis. Currently a dozen medications are available which have been shown in clinical trials to reduce the risk of suffering more exacerbations of MS, and evidence is increasing that early treatment reduces or delays the risk of developing secondary progressive MS, which usually occurs years after onset of the relapsing-remitting form.
Unfortunately, this success in a protective therapy has not been matched by treatments to reverse impairment which is already present or to arrest the progression of disability that occur in progressive forms of MS. To meet this need, research is expanding on several fronts, including remyelination and stem cell treatments.
Remyelination and myelin repair are terms for restoring myelin to the nerve fibers in the central nervous system. Myelin is the fatty substance that is wrapped around nerve fibers in the brain, spinal cord and optic nerves, much like insulation encases an electrical wire. Myelin is necessary for nerve fibers to conduct impulses normally, and it is also necessary for nourishing the nerve fiber and keeping it alive. Destruction of myelin by immune cells slows or blocks nerve impulses, resulting in the symptoms of multiple sclerosis, including loss of vision or impairment of walking, bladder function, coordination and sensation, for example. After a period of time, the nerve fiber which has lost its myelin deteriorates and dies.
Conceptually, putting myelin back on the nerves after damage has occurred should make them work again. The challenge is how to do it and when to do it. In fact, myelin repair occurs naturally after an exacerbation of MS, though it may be only partial, and it becomes less and less effective over time because the nerve fiber eventually dies. Examples of strategies to restore myelin are as follows:
- Anti-Lingo antibody. Lingo is a protein which turns off the production of myelin by cells called oligodendrocyte progenitor cells. Without such inhibition, these cells could conceivably make far more myelin than is needed. Anti-Lingo antibody knocks out the Lingo so that the Lingo can no longer suppress the production of myelin. In the RENEW trial, the antibody was given to patients who were experiencing attacks of optic neuritis. Using visual evoked potentials to measure optic nerve conduction, the investigators found that rate and degree of recovery of the optic nerve improved.
- Remyelinating antibody developed by Moses Rodriguez at Mayo Clinic and in a small clinical trial may put myelin back on nerves.
- Remyelination trials are underway, looking for substances that make myelin grow, and more than 40 candidate drugs are in the pipeline, many of them common drugs used for other things, including fluoxetine, phenytoin, metformin, clemastine.
Stem cell science is another approach to treatment in multiple sclerosis as well as many other disorders. (Go to http://stemcells.nih.gov/info/basics/pages/basics1... for extensive information on stem cells). Every cell in the body is highly specialized to perform a particular function. Muscle cells contract and produce movement, cells in endocrine glands produce hormones, cells in the eye turn light into nerve impulses, and in the nervous system, neurons conduct nerve impulses, while other cells protect and nourish those neurons. A stem cell is a cell which has not yet been committed to a specific function and has the potential to develop into any type of cell in the body, including, conceivably, the neurons and myelin and other cells which support the neurons. Stem cell science is the study of how to produce and guide an uncommitted stem cell to become a specialized type of cell which can perform a specific function.
Stem cells may be instrumental in multiple sclerosis in several different ways.
- Bone marrow stem cells (hematopoietic stem cells) have been used for a long time to replace the diseased bone marrow in disorders such as multiple myeloma or some types of cancers. Since cells of the immune system originate in the bone marrow, and since dysfunction in immune cells is an underlying cause of damage to myelin and neurons in multiple sclerosis, a strategy that has actually been under investigation in MS for a long time has been to replace the immune system in a person with MS with a new immune system that is not intent on causing this damage. To do this, the existing bone marrow is destroyed by radiation and chemotherapy, and hematopoietic stem cells are then introduced and repopulate the marrow. The new immune system which arises from the new marrow does not recognize the myelin and neurons to be enemies, so the cycle of immune attack on those cells is interrupted. While clinical trials are under way using this technique, the treatment is not without risk, since radiation and chemotherapy and other drugs which are necessary as part of the process may have side effects. Ongoing trials are designed to determine what percentage of patients benefit from the treatment and what the pitfalls might be. Additionally, in the years that hematopoietic stem cell therapy has been under investigation, many new and increasingly effective drugs for treating MS have been developed, so the risks and benefits of stem cell therapy must be compared to the risks and benefits of those drugs.
- Stem cells to replace damaged cells in the brain and spinal cord is another approach but is still much more theoretical and in very early stages of research. A consortium of 3 centers in New York (NYSTEM) is planning a trial for surgically implanting stem cells which can be directed to produce myelin into selected areas of the brain to see if they will spread and remyelinate demyelinated nerve pathways.
- A variety of techniques are conceivable for using stem cells not only to replace myelin but to reduce inflammation and alter other processes in the balance between damage and repair in MS.
Despite claims on the internet, stem cell therapy for MS is in a very early research phase. At virtually every major MS research meeting, the speakers on stem cell treatments underscore the fact that stem cell treatment should not be undertaken outside of approved clinical trials. Although internet promotions make it look like stem cell treatment is here and is straightforward, many, many uncertainties exist about which of several types of stem cells to use, how to administer them (inject into blood stream, inject into spinal fluid, implant into brain) and an infinite number of details about how to instruct those stem cells to perform the desired function. And as with any medical treatment, the negative effects must be identified, such as paradoxically stirring up processes in the immune system that are harmful while trying to introduce processes that are helpful.
We are in an incredibly exciting time for finding solutions to multiple sclerosis, and clearly the problem of progressive multiple sclerosis is coming into the spotlight with increased basic laboratory and clinical research.
Movement, Reasons to Stay Active When You have Multiple Sclerosis
According to the Centers for Disease Control and Prevention (CDC), “regular physical activity is one of the most important things you can do for your health”. Exercise is associated with some pretty amazing benefits1-3 including:
- Weight loss
- Reduced risk of:
- Cardiovascular disease, such as heart disease or stroke
- Type 2 diabetes
- Metabolic syndrome
- Cancer; specifically colon, breast, endometrial, and lung cancers
- Reduced risk of mental health symptoms, or can be helpful in managing stress
- Better sleep
- More energy, less fatigue
- Improved sexual functioning; specifically increased arousal in women and fewer problems with erectile dysfunction in men
- Improved cognition, especially executive functioning
- Stronger bones and muscles
- Improved quality of life
- Longer life
Several decades ago, individuals with MS were discouraged from physical activity. At that time it was, inaccurately, thought that rigorous exercise could worsen neurologic symptoms. We now know these recommendations were incorrect. In fact, sedentary behavior may lead to even more negative health outcomes for persons with MS, such as cardiovascular disease and reduced mobility.4
Exercise is one of the hottest topics in multiple sclerosis research. Aerobic training, strength training, and even stretching are associated with improvements in walking speed, balance, fatigue, mood, muscle strength, chronic pain, quality of life, and cognition.5-7 Exercise even seems to have a direct impact on the underlying disease process, including reduced relapse rates.8, 9
Introducing exercise is not always easy, but there are a number of activities and options to get started. Walking, outside or on a treadmill, has been shown to improve walking speed, endurance, and balance. Even one 20-minute walking session can improve mood.10 If you use a treadmill, try walking with an uphill or downhill grade, which may help improve balance and gait.11 Pilates and yoga, including modified versions for individuals that utilize a wheelchair for mobility, can help improve mood, posture, walking speed, balance, core strength, arm and leg muscle strength, and decrease chronic pain.6, 10, 12-14 Aquatic exercise, such as swimming or water aerobics, demonstrates similar improvements. If balance and mobility are barriers, try a stationary, arm, or recumbent bike. There are also a number of adapted exercise videos available online; many specifically for persons with MS. Not sure where to start? Try consulting a physical therapist or talk with your doctor. Most importantly, experiment until you find an activity that works for you, and have fun!
Mindfulness-Based Interventions in Multiple Sclerosis
As previously discussed, research has continued to grow in the area of myelin repair, and we now know more about the significant benefits of daily movement and exercise in maintaining healthy physical, psychological, and cognitive functioning in MS. At the same time, it is important to remember that even with these promising interventions, living with MS often means coping with stressful circumstances, experiencing difficult emotions, and facing uncertainty about the future. In order to better understand and address these daily challenges, MS researchers and patients have become increasingly interested in mindfulness-based interventions for reducing stress and improving overall quality of life.
Although mindfulness began as a Buddhist meditation practice over 2400 years ago, it only recently (1970s-2000s) gained attention in the western world as an effective psychological intervention. Through the works of prominent mindfulness researchers (e.g., Jon Kabat-Zinn, PhD; Marsha Linehan, PhD; and Steven Hayes, PhD), mindfulness has been incorporated into a number of evidence-based psychological treatments, including Mindfulness-Based Stress Reduction (MBSR), Mindfulness-Based Cognitive Therapy (MBCT), Dialectical Behavioral Therapy (DBT), and Acceptance and Commitment Therapy.
Mindfulness is often defined as non-judgmental, purposeful awareness/attention in the present moment. For people with MS, it is not uncommon to become “stuck” in unhelpful patterns of thinking that can worsen stress and reduce overall quality of life. These unhelpful thoughts often focus on the past or future, rather than the present, or on aspects of the disease that are out of one’s control (e.g., “Life used to be so great, but now MS has ruined everything I care about.” “My MS will just keep getting worse and there’s nothing I can do about it.”) Mindfulness practice works to identify and acknowledge unpleasant thoughts and emotions as they arise, without becoming attached to or trapped in them. Importantly, mindfulness offers a unique set of skills that, with daily practice and the help of a trained mental health professional, can be successfully developed and integrated into one’s daily life.
Although mindfulness in MS is a relatively new area of research, a handful of MS studies have identified mindfulness as an effective intervention. A systematic review by Simpson and colleagues (2014) concluded that mindfulness-based interventions resulted in significant improvements quality of life, mental health, and some measures of physical health for people with MS. Given the infancy of this research, however, further studies are needed to identify which types of mindfulness interventions are most helpful and which patients may benefit most from this type of treatment. For more information on mindfulness, please see the suggested references below.
Movement, Reasons to Stay Active When You have Multiple Sclerosis
- Mayo C. Exercise: 7 benefits of regular physical activity 2016. Available from: URL: http://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise/art-20048389?pg=1.
- NIHSeniorHealth. Exercise: Benefits of Exercise. 2015.
- CDC. The Benefits of Physical Activity 2016 June 4, 2015. Available from: URL: http://www.cdc.gov/physicalactivity/basics/pa-health/.
- Marrie RA, Hanwell H. General health issues in multiple sclerosis: comorbidities, secondary conditions, and health behaviors. Continuum (Minneap Minn) 2013;19(4 Multiple Sclerosis):1046-57.
- Beier M, Bombardier CH, Hartoonian N, Motl RW, Kraft GH. Improved physical fitness correlates with improved cognition in multiple sclerosis. Arch Phys Med Rehabil 2014;95(7):1328-34.
- Kalron A, Rosenblum U, Frid L, Achiron A. Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: A randomized controlled trial. Clin Rehabil 2016.
- Kierkegaard M, Lundberg I, Olsson T, Johansson S, Ygberg S, Opava C et al. High-intensity resistance training in multiple sclerosis - An exploratory study of effects on immune markers in blood and cerebrospinal fluid, and on mood, fatigue, health-related quality of life, muscle strength, walking and cognition. J Neurol Sci 2016;362:251-7.
- Deckx N, Wens I, Nuyts AH, Hens N, De Winter BY, Koppen G et al. 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis. Mediators Inflamm 2016;2016:6789276.
- Pilutti LA, Platta ME, Motl RW, Latimer-Cheung AE. The safety of exercise training in multiple sclerosis: a systematic review. J Neurol Sci 2014;343(1-2):3-7.
- Ensari I SB, Motl RW. Effects of Single Bouts of Walking Exercise and Yoga on Acute Mood Symptoms in People with Multiple Sclerosis. - PubMed - NCBI. Int J MS Care 2016;18(1):1-8.
- Samaei A, Bakhtiary AH, Hajihasani A, Fatemi E, Motaharinezhad F. Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial. Int J MS Care 2016;18(1):34-41.
- van der Linden ML, Bulley C, Geneen LJ, Hooper JE, Cowan P, Mercer TH. Pilates for people with multiple sclerosis who use a wheelchair: feasibility, efficacy and participant experiences. Disabil Rehabil 2014;36(11):932-9.
Mindfulness-Based Interventions in Multiple Sclerosis
- Dimidjian, S., Kleiber, B. V., & Segal, Z. V. (2009). Mindfulness-based cognitive therapy. Cognitive and behavioral theories in clinical practice, 307-30.
- Hayes, S. C. (2004). Acceptance and Commitment Therapy and the New Behavior Therapies: Mindfulness, Acceptance, and Relationship.
- Kabat-Zinn, J. (2009). Wherever you go, there you are: Mindfulness meditation in everyday life. Hachette Books.
- Robins, C. J. (2003). Zen principles and mindfulness practice in dialectical behavior therapy. Cognitive and behavioral practice, 9(1), 50-57.
- Simpson, R., Booth, J., Lawrence, M., Byrne, S., Mair, F., & Mercer, S. (2014). Mindfulness based interventions in multiple sclerosis-a systematic review. BMC neurology, 14(1),
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